19 Immune Tolerance Flashcards
What is meant by immune tolerance?
Unresponsive ness to an antigen due to previous exposure to the antigen
What is meant by autoimmunity
Destruction of self antigens by the body
How is immune tolerance completed?
The B and T cells that express self antigens must be downgraded or destroyed. Several mechanisms are involved in this including central and peripheral response
How does central tolerance develop?
The thymus plays a big role in eliminating T cells with high affinity to self antigens. Bone marrow is important in B cell tolerance o
What occurs during peripheral tolerance?
Mature lymphocytes that recognise self antigens in peripheral tissue become incapable of activation or die by apoptosis
What are the mechanisms of immunological tolerance?
Anergy- functional unresponsiveness
Antigen- recognition with co-stimulation
Treg suppression
Deletion(cell death)
Some self antigens are sequestered from the immune system by anatomic barriers
How can molecules overcome peripheral tolerance?
Inappropriate of self antigens
Inappropriate or increased local expression of co-stimulatory molecules
Alterations in the way self molecules are presented to the immune system
More likely to happen during inflammation or cell damage
Self peptides can be altered by virus’, free radicals or ionising radiations
What contributes to autoimmune disease?
Genetics
Infection
Environmental factors
What are natural antibodies?
B1 cells secrete natural antibodies, these can cross react with a and B blood groups to destroy blood not of that type
What contributes to T cells not being able to broken down properly
Inherited HLA that is damaged and won’t recognise self antigens
Poor expressions of self antigens in the thymus
Infections
Drugs
What genetic factors cause autoimmune disease?
Clusters within families of certain polymorphisms that increases the chance of these diseases
What is AI-RE?
Autoimmune regulator acts to eliminate T cells, in its abscence self antigen T cells can be eliminated
What environmental factors cause autoimmunity?
Drugs-molecular mimicry, up regulation of co stimulation,
Viruses- molecular mimicry, genetic variation in drug metabolism
UV radiation- trigger for skin inflammation, modification of self antigen
Give some examples of molecular mimicry?
Group A strep- antigen found in cardiac muscle, can lead to rheumatic fever
Coxsackie B4 nuclear protein- pancreatic islet cell gultamate decarboxylase leads to type 1 diabetes
Campylobacter jejuni glycoproteins- myelin associated gangliosides and glycolipids- leads to guillian Barre syndrome
How does infection lead to autoimmunity?
Antigen presenting cells are activated, expressing c stimulation. This may cause self antigens to react due to molecular mimicry
Give some examples of hormone receptors that cause autoimmune disease
Give some examples of neurotransmitter receptors that are affected by autoimmune disease?
TSH receptrors–> hyperthyroidsim or hypothyroidism
Insulin receptors–> hyper/hypoglycaemia
Acetylcholine receptors-myasthenia gravis
Give some examples of cell adhesion molecules that are affected by autoimmune diseases
Give some examples of plasma proteins that can be affected by autoimmune disease
Give some examples of Other cell surface antigens that can be affected by autoimmune disease
Epidermal cell adhesion molecules–> blistering skin disease
Factor VIII- acquried heamophilia
Beta-2 glycoprotein I and other anticoagulant proteins
Red blood cells (multiple antigens)–>heamolytic anaemia
Platelets–> thrombocytopenia purpura
Give some examples of intracellular enzymes that cause autoimmune disease?
Thyroid peroxidase- thyroiditis, hypothyroidism
Steroid 21-hydroxylase (adrenal cortex)- adrenocortical failure (addisons)
Glutamate decarboxylase (beta cells of the pancreatic islets)- autoimmune diabetes
Lysosomal enzymes (phagocytic cells)- systemic vasculitis
Mitochondrial enzymes (pyruvate dehydrogenase)- primary biliary cirrhosis
Give some examples of intracellular molecules that are involved in trancription and translation?
Double stranded DNA, Histones- SLE
Topoisomerase I- Diffuse scleroderma
Amino- acetly t-RNA synthases- polymositis
Centromere proteins- limited scleroderma
What contributes to an increasing risk of developing SLE?
Inheritance of HLA-DR2 Inheritance f impaired DNA clearance Infection leading to apoptosis and interferon secretion Drugs that reduce DNA clearance Unknown mechanisms Exposure to UV light Pregnancy
How do you treat autoimmune disease?
Suppress damaging immune response ( steroids, immuno-therapy)
Replace the function of the damaged organ (TSH, insulin administration)
